The bacterial cell surface functions both in the physiology of the cell but also in the interaction of the cell with its environment. For human pathogens, these include adhesion, host invasion and subsequent evasion of host defense mechanisms such as killing by serum, phagocytosis, and interactions with specific antibodies. The amount and specific structure of individual bacterial cell surface components determine these properties. For example, two structures found on the surface of Gram-negative bacteria are lipopolysaccharide (LPS) and capsular polysaccharide. LPS that contain long side chains of 0-antigen polysaccharide are found on bacteria that resist bacteriocidal effects of serum. Similarly, the capsular polysaccharide may serve to protect the bacterial cell against the killing effects of serum. This protection is due to the ability of these polysaccharides to interfere with the rate and/or extent of deposition of the complement component C3b on the bacterial cell surface. This deposition is a prerequisite for subsequent events leading to the death of the bacterial cell. Salmonellae typhi is the agent responsible for typhoid fever in man and the surface of these cells is coated with two polysaccharides, LPS and the capsular poly- saccharide called the Vi-antigen. We have examined the relative roles of the Vi-antigen and the 0-antigen polysaccharide side chains of LPS in resistance of iogenic Vi+/- strains of Salmonellae typhi to determine the relative contributions of surface structures in the protection of the cell against serum killing and phagocytosis. We found the Viantigen had no influence on resistance to serum killing but decreases the relative rate of phagocytosis of Vi+ cells. We suggest Vi-antigen may interfere with the recognition of complement on the bacterial cell surface by phagocyte receptors. We also examined the effect of aspirin on antibiotic sensitivity of bacteria, and find that cells grown in the presence of 1-5 mM aspirin (or tylenol) become resistent to levels of antibiotics commonly achieved during therapy. This resistance is due to inhibition of expression of cell surface protein, the OmpF porin, that functions the uptake of the antibiotic. This suggests that administration of aspirin or tylenol with commonly prescribed antibiotics be avoided.